Ever since the development of norfloxacin, significant effort has been devoted worldwide to developing quinolone carboxylic acid-based antibacterial agents. These antibacterial agents are now used as an effective cure for infectious diseases.
The recent emergence of drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP) and vancomycin-resistant enterococci (VRE), poses a serious threat to the treatment of infectious diseases. Most of these drug-resistant bacteria are gram-positive bacteria, which are less susceptible to traditional quinolonecarboxylic acid-based antibacterial agents. Apparently, these antibacterial agents can no longer serve as an effective countermeasure to gram-positive drug-resistant bacteria. The increase in the occurrence of quinolone-resistant Staphylococcus aureus (QRSA) resistant to quinolonecarboxylic acid-based antibacterial agents poses another threat to the treatment of infectious diseases.
While certain quinolonecarboxylic acid derivatives having 3-cyclopropylaminomethyl-1-pyrrolidinyl group are known compounds, the antibacterial activity of these compounds against drug-resistant bacteria still remains unclear, as does the safety of the compounds (Patent Documents 1 and 2). No studies have reported the synthesis and the biological activity of quinolonecarboxylic acid derivatives having 4-substituted-3-cyclopropylaminomethyl-1-pyrrolidinyl group.
[Patent Document 1] Japanese Patent Laid-Open Publication No. Sho 59-67269
[Patent Document 2] Pamphlet of WO97/400